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dc.contributor.authorWesolowska-Andersen, A
dc.contributor.authorBrorsson, CA
dc.contributor.authorBizzotto, R
dc.contributor.authorMari, A
dc.contributor.authorTura, A
dc.contributor.authorKoivula, R
dc.contributor.authorMahajan, A
dc.contributor.authorVinuela, A
dc.contributor.authorTajes, JF
dc.contributor.authorSharma, S
dc.contributor.authorHaid, M
dc.contributor.authorPrehn, C
dc.contributor.authorArtati, A
dc.contributor.authorHong, MG
dc.contributor.authorMusholt, PB
dc.contributor.authorKurbasic, A
dc.contributor.authorDe Masi, F
dc.contributor.authorTsirigos, K
dc.contributor.authorPedersen, HK
dc.contributor.authorGudmundsdottir, V
dc.contributor.authorThomas, CE
dc.contributor.authorBanasik, K
dc.contributor.authorJennison, C
dc.contributor.authorJones, A
dc.contributor.authorKennedy, G
dc.contributor.authorBell, J
dc.contributor.authorThomas, L
dc.contributor.authorFrost, G
dc.contributor.authorThomsen, H
dc.contributor.authorAllin, K
dc.contributor.authorHansen, TH
dc.contributor.authorVestergaard, H
dc.contributor.authorHansen, T
dc.contributor.authorRutters, F
dc.contributor.authorElders, P
dc.contributor.authort'Hart, L
dc.contributor.authorBonnefond, A
dc.contributor.authorCanouil, M
dc.contributor.authorBrage, S
dc.contributor.authorKokkola, T
dc.contributor.authorHeggie, A
dc.contributor.authorMcEvoy, D
dc.contributor.authorHattersley, A
dc.contributor.authorMcDonald, T
dc.contributor.authorTeare, H
dc.contributor.authorRidderstrale, M
dc.contributor.authorWalker, M
dc.contributor.authorForgie, I
dc.contributor.authorGiordano, GN
dc.contributor.authorFroguel, P
dc.contributor.authorPavo, I
dc.contributor.authorRuetten, H
dc.contributor.authorPedersen, O
dc.contributor.authorDermitzakis, E
dc.contributor.authorFranks, PW
dc.contributor.authorSchwenk, JM
dc.contributor.authorAdamski, J
dc.contributor.authorPearson, E
dc.contributor.authorMcCarthy, MI
dc.contributor.authorBrunak, S
dc.date.accessioned2022-03-06T02:03:03Z
dc.date.available2022-03-06T02:03:03Z
dc.date.issued2022-01-18
dc.identifier.issn2666-3791
dc.identifier.otherPMC8784706
dc.identifier.other35106505
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334703
dc.description.abstractThe presentation and underlying pathophysiology of type 2 diabetes (T2D) is complex and heterogeneous. Recent studies attempted to stratify T2D into distinct subgroups using data-driven approaches, but their clinical utility may be limited if categorical representations of complex phenotypes are suboptimal. We apply a soft-clustering (archetype) method to characterize newly diagnosed T2D based on 32 clinical variables. We assign quantitative clustering scores for individuals and investigate the associations with glycemic deterioration, genetic risk scores, circulating omics biomarkers, and phenotypic stability over 36 months. Four archetype profiles represent dysfunction patterns across combinations of T2D etiological processes and correlate with multiple circulating biomarkers. One archetype associated with obesity, insulin resistance, dyslipidemia, and impaired β cell glucose sensitivity corresponds with the fastest disease progression and highest demand for anti-diabetic treatment. We demonstrate that clinical heterogeneity in T2D can be mapped to heterogeneity in individual etiological processes, providing a potential route to personalized treatments.
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101766894
dc.sourceessn: 2666-3791
dc.subjectType 2 diabetes
dc.subjectDisease Progression
dc.subjectArchetypes
dc.subjectPrecision Medicine
dc.subjectPatient Stratification
dc.subjectMulti-omics
dc.subjectPatient Clustering
dc.subjectSoft-clustering
dc.subjectGlycaemic Deterioration
dc.subjectHumans
dc.subjectDiabetes Mellitus, Type 2
dc.subjectGenetic Predisposition to Disease
dc.subjectRisk Factors
dc.subjectFollow-Up Studies
dc.subjectGenomics
dc.subjectPhenotype
dc.subjectAdult
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.titleFour groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: An IMI DIRECT study
dc.typeArticle
dc.date.updated2022-03-06T02:02:58Z
prism.issueIdentifier1
prism.publicationNameCell Reports Medicine
prism.volume3
dc.identifier.doi10.17863/CAM.82121
dcterms.dateAccepted2021-11-23
rioxxterms.versionofrecord10.1016/j.xcrm.2021.100477
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidBrage, Soren [0000-0002-1265-7355]
dc.identifier.eissn2666-3791
pubs.funder-project-idWellcome Trust (098381, 102820/Z/13/Z, 090532 , 106130, 212259 , 098381 , 090532, 106130 , 212259, 203141, 203141)
pubs.funder-project-idNational Institute for Health Research (NIHR) (NF-SI-0508-10112)
cam.issuedOnline2022-01-04


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International